Measurement of TPMT activity is encouraged prior to commencing the treatment of patients with thiopurine drugs such as azathioprine, 6-mercaptopurine and 6-thioguanine. Patients with low activity (10% prevalence) or especially absent activity (prevalence 0.3%) are at a heightened risk of drug-induced bone marrow toxicity due to accumulation of the unmetabolised drug. Reuther et al. found that about 5% of all thiopurine therapies will fail due to toxicity. This intolerant group could be anticipated by routine measurement of TPMT activity. There appears to be a great deal of variation in TPMT mutation, with ethnic differences in mutation types accounting for variable responses to 6MP.
Genetic variants of TPMT have also been associated with cisplatin-induced ototoxicity in children. TPMT is now listed as a pharmacogenomic biomarker for adverse drug reactions to cisplatin by the FDA.
^ abOncea I, Duley J. (2008). "Pharmacogenetics of Thiopurines.". Goodman & Gilman's “The Pharmacological Basis of Therapeutics”, published McGraw-Hill's Access Medicine (on-line) (11th ed.). Chapter 38.
Reuther LO, Vainer B, Sonne J, Larsen NE (January 2004). "Thiopurine methyltransferase (TPMT) genotype distribution in azathioprine-tolerant and -intolerant patients with various disorders. The impact of TPMT genotyping in predicting toxicity". Eur. J. Clin. Pharmacol.59 (11): 797–801. doi:10.1007/s00228-003-0698-8. PMID14634700..
Krynetski EY, Tai HL, Yates CR, et al. (1997). "Genetic polymorphism of thiopurine S-methyltransferase: clinical importance and molecular mechanisms.". Pharmacogenetics6 (4): 279–90. doi:10.1097/00008571-199608000-00001. PMID8873214.
Corominas H, Baiget M (2004). "Clinical utility of thiopurine S-methyltransferase genotyping.". American journal of pharmacogenomics : genomics-related research in drug development and clinical practice4 (1): 1–8. doi:10.2165/00129785-200404010-00001. PMID14987117.
Coulthard SA, Matheson EC, Hall AG, Hogarth LA (2005). "The clinical impact of thiopurine methyltransferase polymorphisms on thiopurine treatment.". Nucleosides Nucleotides Nucleic Acids23 (8–9): 1385–91. doi:10.1081/NCN-200027637. PMID15571264.
Honchel R, Aksoy IA, Szumlanski C, et al. (1993). "Human thiopurine methyltransferase: molecular cloning and expression of T84 colon carcinoma cell cDNA.". Mol. Pharmacol.43 (6): 878–87. PMID8316220.
Glauser TA, Nelson AN, Zembower DE, et al. (1993). "Diethyldithiocarbamate S-methylation: evidence for catalysis by human liver thiol methyltransferase and thiopurine methyltransferase.". J. Pharmacol. Exp. Ther.266 (1): 23–32. PMID8392551.
Szumlanski C, Otterness D, Her C, et al. (1996). "Thiopurine methyltransferase pharmacogenetics: human gene cloning and characterization of a common polymorphism.". DNA Cell Biol.15 (1): 17–30. doi:10.1089/dna.1996.15.17. PMID8561894.
Krynetski EY, Fessing MY, Yates CR, et al. (1998). "Promoter and intronic sequences of the human thiopurine S-methyltransferase (TPMT) gene isolated from a human PAC1 genomic library.". Pharm. Res.14 (12): 1672–8. doi:10.1023/A:1012111325397. PMID9453052.